Vertebral fractures (VFs) have been associated with future fractures, yet few studies have evaluated whether this pertains to VFs available for identification on routine radiological imaging. We sought to evaluate the risk of subsequent fractures in subjects with VF identified opportunistically on computed tomography (CT) scans performed as part of routine clinical practice. From the radiology database of Holbæk Hospital we identified the first CT scan including the thorax and/or abdomen of 2000 consecutive men and women aged 50 years or older, performed from January 1, 2010 onward. The scans were assessed in a blinded approach to identify chest and lumbar VF, and these data linked to national Danish registers. Subjects were excluded if treated with an osteoporosis medication (OM) in the year prior to baseline (date of CT), and the remaining subjects with VF matched on age and sex in 1:2 ratio against subjects with no VF. We found that the risk of major osteoporotic fractures (hip, non-cervical vertebral, humerus, and distal forearm fractures) was higher for subjects with VF than without VF: incidence rates (IRs) were 32.88 and 19.59 fractures per 1000 subject-years, respectively, and the adjusted hazard ratio (HRadj) was 1.72 (95% confidence interval [CI], 1.03-2.86). Subsequent hip fracture IRs were 16.75 and 6.60; HRadj 3.02 (95% CI, 1.39-6.55). There were no significant differences in other fracture outcomes (including a pooled estimate of any subsequent fracture, except face, skull, and fingers: IRs 41.52 and 31.38; HRadj 1.31 [95% CI, 0.85-2.03]). Our findings suggest that subjects undergoing routine CT scans including the chest and/or abdomen are a high risk population in terms of fracture risk. Even within this group, subjects with VF are at higher risk of future major osteoporotic fracture (MOF), in particular hip fracture. Hence, systematic opportunistic screening for VF and subsequent fracture risk management is important to reduce the risk of new fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.